Potassium Phosphate, Tribasic → 4-(4-bromo-2-methoxyphenyl)-6-methyl-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

HRID 930897Notes

Reaction equation

HRID 930897 reaction equation
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[C:5]2[CH:17]=[CH:18][N:19]([S:20]([C:23]3[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:4]=2[C:3]1=[O:30].[Br:31][C:32]1[CH:37]=[CH:36][C:35](I)=[C:34]([O:39][CH3:40])[CH:33]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:31][C:32]1[CH:37]=[CH:36][C:35]([C:6]2[C:5]3[CH:17]=[CH:18][N:19]([S:20]([C:23]4[CH:24]=[CH:25][C:26]([CH3:27])=[CH:28][CH:29]=4)(=[O:21])=[O:22])[C:4]=3[C:3](=[O:30])[N:2]([CH3:1])[CH:7]=2)=[C:34]([O:39][CH3:40])[CH:33]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 468357314-Bromo-1-iodo-2-methoxybenzeneHCID 867210626-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

Product 1

HCID 867210614-(4-bromo-2-methoxyphenyl)-6-methyl-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-oneYield 88%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

The product from Example 6a (0.2 g, 0.467 mmol), 4-bromo-1-iodo-2-methoxybenzene (0.16 g, 0.514 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.013 g, 0.014 mmol), 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamante (0.014 g, 0.047 mmol) and potassium phosphate tribasic (0.347 g, 1.634 mmol) were combined and sparged with argon for 15 minutes. Meanwhile a solution of 4:1 dioxane/water (7.5 mL) was sparged with nitrogen for 15 minutes and transferred by syringe into the reaction vessel under argon. The mixture was stirred at ambient temperature for 20 minutes and partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride, dried (Na2SO4), treated with 3-mercaptopropyl functionalized silica gel for twenty minutes, filtered, and concentrated. Purification by chromatography (silica gel, 10-80% ethyl acetate in heptanes) afforded the title compound (0.2 g, 88%)

Workup

  1. customsparged with argon for 15 minutes
  2. customMeanwhile a solution of 4:1 dioxane/water (7.5 mL) was sparged with nitrogen for 15 minutes
  3. customtransferred by syringe into the reaction vessel under argon
  4. custompartitioned between ethyl acetate and water
  5. washThe organic layer was washed with saturated aqueous sodium chloride
  6. dry with materialdried (Na2SO4)
  7. additiontreated with 3-mercaptopropyl functionalized silica gel for twenty minutes
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by chromatography (silica gel, 10-80% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-a1c4891a6f6a4921822e8846d47b5948
Source dataset
uspto-grants-2016_03
Patent number
US09296741B2

Reaction notes

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